Zellweger Syndrome

Zellweger syndrome

A genetic disorder, also called the cerebrohepatorenal syndrome, characterized by the reduction or absence ofperoxisomes (cell structures that rid the body of toxic substances) in the cells of the liver, kidneys, and brain.Zellweger syndrome is one of a group of disorders called the leukodystrophies, all of which affect the myelin sheath,the fatty covering which acts as an insulator on nerve fibers in the brain. The most common features of Zellwegersyndrome 
include an enlarged liver, high levels of iron and copper in the blood, and vision disturbances. Someaffected infants may show prenatal growth failure. Symptoms at birth may include lack of muscle tone and aninability to move. Other symptoms may include unusual facial characteristics, mental retardation, seizures, and aninability to suck and/or swallow. Jaundice and gastrointestinal bleeding may also occur. There is no cure forZellweger syndrome and there is no standard course of treatment. Infections are guarded against to prevent suchcomplications as pneumonia and respiratory distress. Other treatment is symptomatic and supportive. Theprognosis (outlook) with Zellweger syndrome is poor. Death usually occurs within 6 months after onset, and may becaused by respiratory distress, gastrointestinal bleeding, or liver failure. The syndrome is caused by mutations(changes) in any of several different genes involved in peroxisome formation. These genes lie on at least twodifferent chromosome locations including chromosome 2 (region 2p15) and chromosome 7 (region 7q21-q22). Thesyndrome is named for the Swiss-born pediatrician Hans Zellweger (1909-1990) who came to the US and for manyyears was at the University of Iowa,
Zellweger syndrome, also called cerebrohepatorenal syndrome, is a rarecongenital disorder characterized by the reduction or absence of functionalperoxisomes in the cells of an individual.[1] It is one of a family of disorders called leukodystrophies. Zellweger syndrome is named after Hans Zellweger(1909–1990), a Swiss-American pediatrician, a professor of pediatrics and genetics at the University of Iowa who researched this disorder.


Zellweger syndrome is one of three peroxisome biogenesis disorders which belong to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD). The other two disorders are neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). Although all have a similar molecular basis for disease, Zellweger syndrome is the most severe of these three disorders.
Zellweger syndrome is associated with impaired neuronal migration, neuronal positioning, and brain development. In addition, individuals with Zellweger syndrome can show a reduction in central nervous system (CNS) myelin (particularly cerebral), which is referred to as hypomyelination. Myelin is critical for normal CNS functions, and in this regard, serves to insulate nerve fibers in the brain. Patients can also show postdevelopmental sensorineuronal degeneration that leads to a progressive loss of hearing and vision.

Zellweger syndrome can also affect the function of many other organ systems. Patients can show craniofacial abnormalities (such as a high forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel),hepatomegaly (enlarged liver), chondrodysplasia punctata (punctate calcification of the cartilage in specific regions of the body), eye abnormalities, and renal cysts.Newborns may present with profound hypotonia (low muscle tone), seizures, apnea, and an inability to eat.
Causes

Zellweger syndrome is an autosomal recessive disorder caused by mutations in genes that encode peroxins, proteins required for the normal assembly of peroxisomes. Most commonly, patients have mutations in the PEX1, PEX2, PEX3, PEX5,PEX6, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, and PEX26 genes.In almost all cases, patients have mutations that inactivate or greatly reduce the activity of both the maternal and paternal copies of one these aforementioned PEXgenes.

As a result of impaired peroxisome function, an individual's tissues and cells can accumulate very long chain fatty acids(VLCFA) and branched chain fatty acids (BCFA) that are normally degraded in peroxisomes. The accumulation of these lipids can impair the normal function of multiple organ systems, as discussed below. In addition, these individuals can show deficient levels of plasmalogens, ether-phospholipids that are especially important for brain and lung function. 

Diagnosis

In addition to genetic tests involving the sequencing of PEX genes.biochemical tests have proven highly effective for the diagnosis of Zellweger syndrome and other peroxisomal disorders. Typically, Zellweger syndrome patients show elevatedvery long chain fatty acids in their blood plasma. Cultured primarily skin fibroblasts obtained from patients show elevated very long chain fatty acids, impaired very long chain fatty acid beta-oxidation, phytanic acid alpha-oxidation, pristanic acidalpha-oxidation, and plasmalogen biosynthesis.

Prognosis

Currently, no cure for Zellweger syndrome is known, nor is a course of treatment made standard. Infections should be guarded against to prevent such complications as pneumonia and respiratory distress. Other treatment is symptomatic and supportive. Patients usually do not survive beyond one year of age

Zellweger syndrome

is the most severe form of a spectrum of conditions called Zellweger spectrum disorders. The signs and symptoms of Zellweger syndrome typically appear during the newborn period and may include poor muscle tone (hypotonia), poor feeding, seizures, hearing loss, vision loss, distinctive facial features, and skeletal abnormalities. Affected children also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys. Children with Zellweger syndrome usually do not survive beyond the first year of life. Zellweger syndrome is caused by mutations in any one of at least 12 genes; mutations in the PEX1 gene are the most common cause. It is inherited in an autosomal recessive manner. There is no cure for Zellweger syndrome; treatment is generally symptomatic and supportive.
Treatment.

  Syp-Zellviris ( 1Teaspoonful Every 6 Hours).